The research objective is the elucidation of the mechanism of action of psychotropic drugs. More specifically we propose to study the possible role of cyclic nucleotides (adenosine 3', 5'-monophosphate and guanosine 3', 5'-monophosphate), cyclic nucleotide-dependent protein kinases, substrate proteins for the protein kinases, and protein phosphatases, in mediating the actions of psychoactive substances. In this connection we propose to study the effect of a variety of neuro-transmitters and psychoactive substances on adenylate cyclase and guanylate cyclase activity in homogenates, on cyclic AMP and cyclic GMP levels in intact brain slices, and on phosphoprotein metabolism in subcellular fractions and slices of brain tissue. In addition, we propose to study the effects of neurotransmitters and of psychoactive drugs on the level of cyclic AMP receptor protein using a recently developed method for measuring this receptor protein. It is our hope that these studies will contribute to a deeper understanding of the use of drug therapy in the treatment of mental illness and to improvements in such therapy.